This is the FDA page on the definition of a breakthrough therapy.

 https://www.fda.gov/regulatory-information/food-and-drug-administration-safety-and-innovation-act-fdasia/fact-sheet-breakthrough-therapies

There has to be preliminary evidence of “substantial” benefit. A little under 50 % of applications are granted.

Could be for STLG2, CHF, GFR, dementia.